Hope for myeloma

Back in the convention centre, the morning’s first lecture came from the US Dana-Farber Cancer Institute’s Professor Kenneth Anderson, a world-leading expert in myeloma, a cancer of the bone marrow. Prof Anderson brought a message of hope for myeloma patients, showing how survival from this less common cancer has doubled over recent decades thanks to advances in treatment and new drugs such as bortezomib (Velcade) and lenalidomide (Revlimid).

But the best is yet to come, as Anderson explained how lab research is informing the development of new combinations of existing drugs as well as brand new targeted agents. He showed slide after slide of exciting, promising data from early stage clinical trials.

These new treatment regimes are being put through their paces in larger trials and, judging by the excitement in Anderson’s voice, they could bring forward a real prospect of long-term survival for myeloma patients of the future.

Getting to grips with the “data firehose”

Professor Judy Garber then spoke about how fast-developing DNA sequencing technologies are giving scientists and clinicians “a genomic view of cancer” to help personalise cancer medicine – a theme we’ve discussed before on the blog.

In her thought-provoking presentation, she talked about the “data firehose” of genetic information doctors are now faced with, and the challenge of using this information to make the best treatment decisions for patients. The sheer volume of genetic information can be daunting, and is only going to increase in the future.

Professor Garber also discussed the ethical issues and challenges raised by genetic sequencing – as in-depth genetic scans become commonplace in the diagnosis of cancer, she says doctors are bound to uncover other medically relevant information about a patient that they may or may not wish to know – like they carry a gene that predisposes them to other medical conditions.

Cancer as an evolutionary process

Next, our own Professor Gerard Evan chaired what he only half-jokingly called “the most important session at the conference”, on cancer evolution. Prof Evan is infectiously enthusiastic about using evolutionary theory to understand how cancer develops and grows – you can watch for yourself an inspirational talk he recently gave to our staff.

Professor Evan talked about the need to “de-mystify and de-mythologise” cancer, removing some of the misconceptions about the disease. First and foremost, he said “cancer is not a single, unitary thing” but a phenomenon that constantly changes and evolves.

He said this explained why some cancer treatments can effectively kill off tumour cells but fail to extend life – evolution allows the cancer to “re-wire its signalling networks” and evolve ways to resist treatment and grow again.

But researchers are now using the tools of evolutionary biology to better understand how cancer grows, to try to improve treatment and prevention of the disease. Three speakers took this baton and ran with it, outlining the latest thinking in this field.

First, Professor Carlo Maley from the University of California discussed how a tumour’s genetic diversity affects how it responds to treatment. His work in lung cancer shows how, as genetic diversity increase within a tumour, it becomes harder to treat.

He wondered whether we could develop cancer prevention strategies that reduce the rate of genetic mutation (as might be possible with aspirin and Barrett’s oesophagus – a fore-runner of oesophageal cancer). And he floated the provocative idea that, instead of aiming to kill tumour cells with cancer treatments – which could inadvertently encourage treatment-resistant cells to grow faster – we could develop strategies to maintain a stable, non-growing tumour.

Next, the Institute of Cancer Research’s Professor Mel Greaves – one of the first researchers in the world to fully highlight cancer’s evolutionary nature – gave us an update on the latest thinking on how leukaemias evolve. Rather than being a single disease, Greaves has shown how leukaemias are actually a collection of sub-clones, all existing within the same patient.

“We often talk about the cancer genome,” he said, “but in reality we need to be talking about a leukaemia patient having ten or more cancer genomes”. He’s now homing in on the source of this ‘variagation’ in leukaemia – cancer stem cells.

Finally, Professor Peter Campbell, from the world-leading Wellcome Trust Sanger Institute in Cambridge, outlined how applying complex maths and statistics to detailed genetic analyses can be used to reconstruct tumours’ histories, and shed light on the processes that cause their DNA to become so profoundly disordered.

From this work – which Professor Evan likened to the task of “trying to do archaeology when someone’s already ploughed the field” – his team have found evidence of distinct processes at work in tumours from different patients, and in tumours from different parts of the body.

Underlining the session’s take-home, somewhat daunting, message, he called the sheer diversity of behaviour and mechanisms they’re uncovering “remarkable”.

Cancer in the developing world

We took a trip around the world just before lunch, with a breakout session on cancer in low- and middle-income countries. The session kicked off with a round-up of what we know about the patterns of cancer cases and deaths in different countries and areas of the world from Cancer Research UK’s Professor Max Parkin. Already, 47 per cent of cancer cases and 55 per cent of cancer deaths happen in low or middle income countries, and this is only set to rise over the coming years as populations get older.

Hope for childhood brain cancers

When it comes to treating childhood cancers, we can’t treat them as ‘small adults’ and that was a running theme through this afternoon’s session on brain tumours in children. Dr Chris Jones, based at The Institute of Cancer Research, opened with the optimism that researchers have begun to feel over the last 12 months in understanding more about the disease, particularly in the discovery that there appear to be unique forms of the disease that affect different ages and how likely a child will survive the disease.

Dr Jones was hopeful that in one form, these discoveries could lead to new targeted treatments.

Dr John Anderson, from Great Ormond Street (GOSH), continued the treatment theme by discussing approaches that will use the body’s own defences to treat brain tumours. Drawing on the experience of treating adult brain tumours, he felt this approach could be used in children.

In the final discussion, Dr Darren Hargrave, also at GOSH, set out the next steps needed to improve treatments. He argued that the design of trials to treat children needed to change, so that new and better treatments could be tested together and against each other to find the ‘winner’.

Biobanking workshop

In one of the day’s most compelling sessions, Wellcome Trust’s Dan Glaser chaired a session looking at the issues around ‘biobanks’ – archives of human tissue used to drive forward research. Aimed at – in Glaser’s words – “stimulating a wider discussion of the issues”, the session covered many sides of the debate.

Firstly, Milan’s Dr Luca Roz highlighted the extraordinary things that can now be achieved with high-quality tissue research, including the ability to create a new type of personalised and sophisticated animal models.

On the flip side, top UK statistician Professor Doug Altman looked back over several decades of research on prognostic biomarkers (tests to that show how well a patient is likely to do) – most of which use patient samples.

Worryingly, Altman said, a huge portion of this research has been poorly carried out, with crucial data missing. For example, only a third of all published studies on neuroblastoma markers are suitable for further (meta-) analysis, and there’s a serious failure to publish negative research. “We need to stop doing this”, he said. “It’s fine if you want to generate more publications, but not if you want to generate knowledge.”

Properly managed and accessed biobanks, together with online registries of biomarker research projects, he argued, had the potential to transform this field by making sure all appropriate data is available to researchers.

Finally, Professor Noel Clarke from the Manchester Cancer Research Centre’s biobank talked about an issue we’ve discussed before – taking samples of a patient’s secondary tumours, or metastases, which will be crucial in understanding how tumours evolve and adapt to treatment.

“Every hospital has a vast amount of tissue in storage, just sitting there, doing nothing,” he said, “and also you’ll have a large amount of data on what happened to those patients. It’s possible, with a little work, to allow access to that data and harness it for research.” With proper thought, planning and consent, he argued, this can be harnessed to do exquisitely detailed ‘bench-to-bedside’ research to understand cancer.

These talks led to one of the most lively discussions of the conference so far, with doctors complaining of ‘consent bloat’ – the fact that their patients are often asked to consent to many different research projects – while patients present expressed their hope that problems could be solved.

Understanding cancer cells

A packed afternoon session brought seven short talks – mostly from Cancer Research UK scientists – getting to grips with the molecular “nuts and bolts” that make cancer cells work.

The researchers covering topics as diverse as blood flow in neuroblastoma (a childhood nerve tissue cancer), drug resistance in bowel cancer, gene faults that drive kidney cancer, testing eyebrows to see how chemotherapy may affect someone, and looking at fruit flies to find out how cells know which way is up.

Listening to these talks, it’s clear that the net is closing on cancer cells, and we are understanding what makes them ‘tick’ on an unprecedented level. By unpicking the complex genetic pathways that drive cancer cells, researchers all over the world can pinpoint likely targets for new treatments.

Although much of the work presented in this session was still at an early stage, it’s vital that Cancer Research UK continues to support fundamental biological research if we’re to find more effective ways to beat cancer in the future.

Towards winning combinations?

In keeping with the theme of tackling cancer’s complexity, an entire afternoon session was dedicated to working out how to combine new drugs to maximum effect. We covered some of these issues last week but session chair Dr Ultan McDermott said there was plenty of cause for optimism given recent developments.

He’s found that targeting a protein called IGFR1 in these patients might be a workable solution, while another option is to target a protein called GATA2 – a strategy that’s leading to clinical trials combining myeloma drug bortezamib and an experimental drug called a ROCK inhibitor.

After the ICR’s Dr Chris Lord showcased some of the latest techniques to find targets for combination therapy, Netherlands’ Professor Lodewyk Wessels then highlighted how combining computational analysis with some of the new online cancer cell databases released this year were proving fruitful ways to find new avenues for research and trials.

Ovarian cancer – a disease of “genetic chaos”?

Professor Iain McNeish opened today’s ovarian cancer session by taking us back to 2008, when the NCRI Cancer Conference last took an in-depth look at the state of diagnosis and teratment for this challenging disease.

Since then, the landscape has changed hugely – we now know that ovarian cancer is at least five distinct diseases, that many of the lab models used to study it aren’t quite what they’re cracked up to be, and that much more needs to be done to control symptoms and improve quality of life for women suffering from it.

UCL’s Professor Usha Menon – who’s running the Cancer Research UK-funded UKCTOCS ovarian cancer screening trial – talked about the challenge of developing effective screening tests and diagnostic techniques for the disease, which are sensitive enough to pick up small cancers that need treatment as early as possible.

Next, Dr Charles Drake explained how gene sequencing techniques are revealing more about the genetic faults driving ovarian cancer. The good news is this information could help to improve treatment for women by tailoring it more effectively to the genetic makeup of their cancer. But the bad news is that sub-dividing patients into smaller and smaller groups makes it difficult to do meaningful clinical trials that provide definite answers about the best treatments.

Finally, Dr James Brenton from the Cancer Research UK Cambridge Rsearch Institute, gave an insight into the “genetic chaos” going on within ovarian cancer cells. He showed how cancer cells change and mutate over time, becoming resistant to treatment.

But while this poses a big challenge for scientists and doctors, new ways of monitoring ovarian cancer progress by analysing tumour DNA in the blood could provide a way to get a handle on what’s going on at a molecular level and make treatment more effective for patients in the future.

A winning combination in rhabdomyosarcoma? Oh YES

Finally, closing an absorbing but exhausting first day, Lee Helman from the US National Cancer Institute told us about the huge strides his team have made in understanding rhabdomyosarcoma – a rare cancer of the muscles.

His group has discovered that a protein called CRKL, which interacts with another protein inside cancer cells called YES, to drive the disease. They’ve found that a drug called dasatinib is able to block this and slow cells’ growth in the lab.

But that’s not all. In a separate project, they confirmed that another protein – IGFR1 – is also able to drive the cell’s growth. Putting two and two together, they’ve made ten – blocking both IGFR1 and YES, they completely halted the growth of cancer cells in the lab. “We’re not there yet – we need to do the trials,” he said. But ongoing research in mice was also showing the same results and, if confirmed, will lead to trials in patients.

Winners

And finally, we’d like to extend warm congratulations to winner Graham Bell, and runners-up Abbie Fearon and Angelos Papaspyropoulos, for their success in the PhD students Hambro poster prize. These are three UK researchers with hugely bright futures. Well done!

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